It is known that LPA receptors bind LPA to transmit a signal into cells and induce various physiological phenomena, such as cell proliferation, dedifferentiation of vascular cells, inhibition of cell proliferation, and the like. Thus, if a human LPA receptor can be provided, not only its application as a medicament or diagnostic drug for vasospasm and the like can be expected using the human LPA receptor per se but also its broad contribution to the development of medicaments, such as screening and evaluation of medicaments, such as a new LPA receptor antagonist and the like, can be expected. Although it is known that plural kinds of LPA receptors are present, all kinds of human LPA receptors have not been isolated yet, and the actions and structures have not been specified.
Cells recognize various physiologically active substances, such as proliferation factors, hormones, neurotransmitters, and the like, via a receptor and response thereto in various manner. LPA receptors which are present on the cell membrane bind to LPA and transmit a signal into the cell via a G protein conjugated with the receptor. Gi, Gq and the like are known as G proteins which can be conjugated with LPA receptors, and it is considered that these receptors take part in responses, such as cell proliferation promoting action or, conversely, proliferation inhibiting action, and the like. Additionally, it has been found that an MAP-kinase system is connected with the downstream of the G protein and the LPA receptors transmit various signals.
Receptors using LPA as the ligand have been isolated from mouse and Xenopus. For example, Tigyi et al. have obtained an LPA receptor, called PSP24 LPA receptor, for the first time from Xenopus oocyte (Proc. Natl. Acad. Sci. U.S.A., 93: 14367-14372 (1996)). Also, another kind of LPA receptor has been cloned from a mouse, which is called vzg-1 (J. Cell. Biol., 135:1071-1083 (1996)).
As human origin LPA receptors, Edg-2 which is a homologue of vzg-1 has been reported (Biochem. Bioph. Res. Commun., 231:619-622 (1997)); however, there are no reports on the PSP24 in human.